Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33

Goshima, Yoshio
Nakamura, Fumio
Strittmatter, Philipp
Strittmatter, Stephen M.

Departments of Neurology and Neurobiology, Yale University School of Medicine, PO Box 208018, New Haven, Connecticut 06520, USA.
(Goshima) Present address: Department of Pharmacology, Yokohama City University, School of Medicine, Yokohama 236, Japan.
(S. Strittmatter) To whom correspondence should be addressed.

Nature 376(6540):p 509-514, August 10, 1995.

COLLAPSIN *RF 1*, a member of the newly recognized semaphorin family *RF 2-4*, contributes to axonal pathfinding during neural development by inhibiting growth cone extension . The mechanism of collapsin action is poorly understood. Here we use a Xenopus laevis oocyte expression system to identify molecules involved in collapsin signalling, because several experiments have raised the possibility that heterotrimeric GTP-binding proteins might participate in these events . A collapsin response mediator protein of relative molecular mass (M_r) 62K (CRMP-62) required for collapsin-induced inward currents in X. laevis oocytes is isolated. CRMP-62 shares homology with UNC-33, a nematode neuronal protein required for appropriately directed axonal extension . CRMP-62 is localized exclusively in the developing chick nervous system. Introduction of anti-CRMP-62 antibodies into dorsal root ganglion neurons blocks collapsin-induced growth cone collapse. CRMP-62 appears to be an intracellular component of a signalling cascade initiated by an unidentified transmembrane collapsin-binding protein.